The present invention relates to an antihypertensive agent comprising a 2-alkynyladenosine as an active ingredient.
Heretofore, adenosine has been used for the treatment of cardiac incompetency, myocardial infarction, arterial sclerosis and angina pectoris. This compound, however, exhibits a strong transient pharmacological effect when taken up into organisms and is known to be rapidly deaminated by adenosine deaminase or taken up into red blood cells and tissues to lose its activity. Adenosine also exhibits a strong suppressive effect on the heart as a side effect.
In order to improve the pharmacological activity of adenosine, impart thereto resistance to adenosine deaminase and mitigate undesirable side effects, a variety of adenosine analogues have been prepared synthetically.
With respect to 2-substituted adenosines, various compounds have been synthesized. For example, 2-alkylthioadenosines, 2-phenylaminoadenosines and the like exhibiting such physiological activities as adenosine deaminase inhibitor effect, coronary vasodilator effect, platelet aggregation inhibitor effect and antiviral effect have so far been obtained.
We have previously synthesized 2-alkynyladenosines of the following formula as 2-substituted adenosine derivatives each having a substituent introduced by a carbon-carbon bond in the 2 position of adenosine: ##STR2## wherein R is Si(CH.sub.3).sub.3, H, Ph, CH.sub.2 OH, CH.sub.2 CH.sub.2 OH, CH(OH)CH.sub.3, (CH.sub.2).sub.2 CH.sub.3, (CH.sub.2).sub.3 CH.sub.3, (CH.sub.2).sub.4 CH.sub.3 or (CH.sub.2).sub.5 CH.sub.3, and have found that these compounds have an inhibitory effect on the I.sub.g E-mediated 48-hr. passive cutaneous anaphylaxis reaction in rats. (Nucleic Acids Research Symposium Series No.12, pp. 5.about.8 (1983) and Chem. Pharm. Bull. Vol. 33, pp. 1766.about.1769 (1985)).
Numerous pharmaceutical preparations have been developed to date as antihypertensive agents. In view of the nature of the disease, pharmaceutical preparations must be administered over a long period of time in many cases. The intake of pharmaceutical preparations over a long period of time may sometimes induce drug resistance therefor or side effects. For this reason, stepwise pharmacotherapy is generally adopted so that a particular pharmaceutical is selected with due consideration for age, severity of hypertension, complications and the like and another pharmaceutical preparation having a different function mechanism is further used in combination depending upon the symptoms.
At present, no pharmaceutical preparations comprising compounds having adenosine skeletons are used as antihypertensive agents, and it would thus be highly profitable for the treatment of hypertension to provide antihypertensive agents comprising adenosine derivatives.